The objective of this proposal is to develop a minimally invasive accurate technique, which can be readily performed under local anesthesia, of selective lymph node biopsy for staging the regional lymph nodes in breast cancer patients. As has been documented for melanoma (l) and supported by preliminary data for breast cancer (this application), the first lymph node to receive lymphatic drainage from a primary tumor (the sentinel node) should be the first site of lymph node metastasis. In preliminary clinical evaluation of breast cancer patients, the sentinel lymph node was 100% predictive of whether the regional lymph nodes did or did not contain metastases. In operable breast cancer patients, peritumoral injection of radioactive colloid will be performed a variable number of hours prior to surgery in order to radiolabel the sentinel lymph node. Different classes of lymphoscintigraphic agents will be tested for optimal labelling of the sentinel lymph node. Gamma probe-guided resection of the sentinel lymph node will be performed in conjunction with a complete 3-level axillary lymph node resection. Pathologic results will be analyzed for the ability of the sentinel lymph node to predict the status of the regional lymph nodes. The data obtained from this study will be used to design and initiate a multi-institutional prospective randomized clinical trial evaluating sentinel lymph node biopsy v. complete axillary lymph node clearance as a staging criteria. Successful completion of this proposal has the potential to improve accuracy and lessen the stress, morbidity, and cost of staging breast cancer in the majority of breast cancer patients.